Fifty studies including 2 reviews (the numbers of participants and study designs were not always stated). 36 looked at monotherapy with troglitazone and 14 at combination therapies.
Monotherapy (not clear how many were vs placebo and how many vs other agents; participant numbers not clear for all of the studies):
In large (n>100) trials conducted in North America using troglitazone (200-800mg/day), FSG was reduced by approximately 11 to 33% and HbA by 5-15% compared with placebo or baseline levels. Fasting serum insulin, C-peptide and triglyceride levels were also typically reduced. The effects of troglitazone on glycaemic control were maintained for over 1 year in one trial. In comparative trials of troglitazone monotherapy versus other agents, troglitazone (600 or 800mg/day) had similar efficacy to glibenclamide (titrated to response) in terms of glycaemic control, although only troglitazone was associated with reductions in serum insulin levels. Comparisons between troglitazone and metoformin using commonly used dosage regimens also showed similar effects on glycaemic control. Similar effects were seen in studies in Japan as compared to North America and Europe.
Combined therapy (2 troglitazone+ glibenclamide, 1 troglitazone+metformin, 5 troglitazone+sulphonylurea, 5 troglitazone+insulin and one unknown combination study):
Concomitant treatment with troglitazone 220-600mg/day, plus either glibenclamide 12mg/day (n=545) or metformin 1000mg twice daily (n=28) was more effective at achieving glycaemic control than monotherapy with these drugs. An open-label extension of troglitazone plus glibenclamide therapy demonstrated that glycaemic control was maintained with combined therapy on a long-term basis (116wks). Other trials of up to 1 year's duration also showed significantly greater reductions in FPG and HbA when troglitazone was added to sulphonylurea in comparison with sulphonylurea monotherapy. The addition of troglitazone (200-600mg/day) to insulin therapy (30 units or more per day) reduced FSG levels, insulin dosage requirements and HbA values, with glycaemic control maintained for up to 23mths in an extension of the largest study (n=286 for the extension study)
Effects on lipid metabolism (6 studies and 1 review):
The effects were generally variable and minor for both mono- and combination therapies, with the exception of consistent reductions in fasting serum triglyceride levels of 13-26%.
Studies in patients with impaired glucose tolerance (3 studies):
Modest but statistically significant reductions in FPG, mean fasting plasma insulin, blood pressure and serum lipids, and improved glucose tolerance were observed with troglitazone compared to placebo in two of the studies. The remaining study did not show an improvement in glucose tolerance, however, insulin sensitivity and circulating insulin levels were improved.
Tolerability:
In clinical trials, the incidence and type of adverse events associated with troglitazone were broadly similar to those observed with placebo. The most frequently observed adverse effects with both troglitazone and placebo were infection (18 vs 22%), headache (11 vs 11%) and pain (10 vs 14%). The rate of patient withdrawal from studies was approximately 4% for both placebo and troglitazone. Unlike sulphonylurea troglitazone was not associated with hypoglycaemic reactions when administered as a monotherapy.